Lung cancer is a leading cause of cancer death worldwide. Lung cancer is responsible for about one-sixth of all cancer deaths. There are two major types of lung cancer: small cell lung cancer and non-small cell lung cancer. Non-small cell lung cancer is the representative lung cancer, which accounts for about 80% of all lung cancer. Adenocarcinoma, squamous cell carcinoma and large cell carcinoma are three types of non-small cell lung cancer. Since there are differences in histological properties as well as prognosis and therapy according to the type of lung cancer, accurate diagnosis is important. Despite the recent advances in cancer therapy, ten-year survival rates of patients with non-small cell lung cancer are 10% or even less. This is because non-small cell lung cancer is generally difficult to diagnose until the disease is relatively advanced. Under present situations, early diagnosis is the most effective method for increasing survival rates of the patients.
A variety of attempts have been made to diagnose lung cancer using markers. Some research reported diagnostic markers of lung cancer through expression of a limited number of target genes and proteins (Hibi et al., Am. J. Pathol. 1999, 155: 711-715; Brechot et al. Eur. J. Cancer 1997, 33: 385-391; Pastor et al., Eur. Respir. J. 1997, 10: 603-609; Morita et al., Int. J. Cancer 1998, 78: 286-292). Also, some reports described the finding of lung cancer marker genes using microarray techniques (Oncogene19—1519; Oncogene23—7734; Oncogene21—7749). However, there is no report involving the possibility of early diagnosis of lung cancer using the presently identified diagnostic markers of lung cancer.
Based on this background, the present inventors, in order to develop biomarkers capable of simply and accurately diagnosing lung cancer, performed primary screening for genes overexpressed only in lung cancer using a DNA chip, and identified highly significant markers by performing RT-PCR. As a result, PKP1, ABCC5, KRT15, KRT14, TRIM29, SERPINB5, TK1, GPX2, MMP1 and ITGB4 genes were identified. When the genes were practically applied to lung cancer samples, they were found to accurately diagnose lung cancer, thereby leading to the present invention.